JPS63421B2 - - Google Patents
Info
- Publication number
- JPS63421B2 JPS63421B2 JP54095255A JP9525579A JPS63421B2 JP S63421 B2 JPS63421 B2 JP S63421B2 JP 54095255 A JP54095255 A JP 54095255A JP 9525579 A JP9525579 A JP 9525579A JP S63421 B2 JPS63421 B2 JP S63421B2
- Authority
- JP
- Japan
- Prior art keywords
- acid
- halogen
- acids
- hydroxyphenylacetic
- present
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 238000007327 hydrogenolysis reaction Methods 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- XQXPVVBIMDBYFF-UHFFFAOYSA-N 4-hydroxyphenylacetic acid Chemical compound OC(=O)CC1=CC=C(O)C=C1 XQXPVVBIMDBYFF-UHFFFAOYSA-N 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 10
- 239000002904 solvent Substances 0.000 description 9
- 238000000034 method Methods 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- IYTUKSIOQKTZEG-UHFFFAOYSA-N (3-chloro-4-hydroxyphenyl)acetic acid Chemical class OC(=O)CC1=CC=C(O)C(Cl)=C1 IYTUKSIOQKTZEG-UHFFFAOYSA-N 0.000 description 5
- 230000003197 catalytic effect Effects 0.000 description 5
- 238000005695 dehalogenation reaction Methods 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 235000019439 ethyl acetate Nutrition 0.000 description 4
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 3
- 125000005907 alkyl ester group Chemical group 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- TXFPEBPIARQUIG-UHFFFAOYSA-N 4'-hydroxyacetophenone Chemical compound CC(=O)C1=CC=C(O)C=C1 TXFPEBPIARQUIG-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 150000001555 benzenes Chemical class 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical class O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- ISPYQTSUDJAMAB-UHFFFAOYSA-N 2-chlorophenol Chemical compound OC1=CC=CC=C1Cl ISPYQTSUDJAMAB-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 229940073735 4-hydroxy acetophenone Drugs 0.000 description 1
- -1 4-hydroxyphenylmalonic acid ester Chemical class 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 239000005456 alcohol based solvent Substances 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- HBMCQTHGYMTCOF-UHFFFAOYSA-N hydroquinone monoacetate Natural products CC(=O)OC1=CC=C(O)C=C1 HBMCQTHGYMTCOF-UHFFFAOYSA-N 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N mandelic acid Chemical class OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- XGDZEDRBLVIUMX-UHFFFAOYSA-N methyl 2-(4-hydroxyphenyl)acetate Chemical compound COC(=O)CC1=CC=C(O)C=C1 XGDZEDRBLVIUMX-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- LLYCMZGLHLKPPU-UHFFFAOYSA-N perbromic acid Chemical compound OBr(=O)(=O)=O LLYCMZGLHLKPPU-UHFFFAOYSA-N 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 229960003424 phenylacetic acid Drugs 0.000 description 1
- 239000003279 phenylacetic acid Substances 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
本発明は抗生物質修飾剤あるいは消炎鎮痛剤の
中間体として有用なフエニル酢酸類、特に4−ヒ
ドロキシフエニル酢酸又はそのアルキルエステル
の新規な製造法を提供するものである。
4−ヒドロキシフエニル酢酸類を製造する方法
として、4−ヒドロキシベンズアルデ法、4−ヒ
ドロキシアセトフエノン法、4−ヒドロキシフエ
ニルマロン酸エステル法等が文献に記載されてい
るが、上記の原料が高価であつたり、目的物の収
率が低いこと等の理由で工業的実施には必ずしも
満足出来ない。
しかるに、本発明者等はかかる問題を解決し工
業的有利に4−ヒドロキシフエニル酢酸等のフエ
ニル酢酸類を製造することを目的として鋭意研究
を重ねた結果、一般式
The present invention provides a novel method for producing phenylacetic acids, particularly 4-hydroxyphenylacetic acid or its alkyl ester, which is useful as an intermediate for antibiotic modifiers or anti-inflammatory analgesics. As methods for producing 4-hydroxyphenylacetic acids, 4-hydroxybenzalde method, 4-hydroxyacetophenone method, 4-hydroxyphenylmalonic acid ester method, etc. are described in the literature. However, it is not always satisfactory for industrial implementation because it is expensive and the yield of the target product is low. However, as a result of extensive research aimed at solving this problem and industrially advantageously producing phenylacetic acids such as 4-hydroxyphenylacetic acid, the present inventors found that the general formula
【式】〔ここでX;ハロ
ゲン、R1、R2、R3;水素又は低級アルキル基、
以下同様〕で表わされるハロゲン置換フエニル酢
酸類、特に3−クロロ−4−ヒドロキシフエニル
酢酸類を脱ハロゲンすることによつて一般式
[Formula] [where X: halogen, R 1 , R 2 , R 3 ; hydrogen or lower alkyl group,
The same applies hereinafter] By dehalogenating halogen-substituted phenylacetic acids, especially 3-chloro-4-hydroxyphenylacetic acids, the general formula
【式】〔R1、R2、R3は前
記同様〕で表わされるフエニル酢酸類、特に4−
ヒドロキシフエニル酢酸類が収率良く得られると
いう新規な事実を見出し本発明を完成するに到つ
た。
一般にベンゼン核に存在するハロゲンを脱ハロ
ゲン化することは公知であるが、本発明の如き一
般式Phenyl acetic acids represented by [Formula] [R 1 , R 2 , R 3 are the same as above], especially 4-
The present invention was completed based on the novel fact that hydroxyphenylacetic acids can be obtained in good yield. It is generally known to dehalogenate the halogen present in the benzene nucleus, but the general formula as in the present invention
【式】で表わされる
ハロゲン置換フエニル酢酸類を脱ハロゲンするこ
とは全く知られていない。本発明ではかかる原料
から脱ハロゲンにより容易に医薬中間体として有
用なフエニル酢酸類が得られるものであり、その
技術の新規性と共に工業的利用価値は極めて大で
ある。
本発明においてR1、R2、R3はそれぞれ水素、
メチル基、エチル基、プロピル基、ブチル基等の
低級アルキル基を示す。更にXはクロル、ブロム
等のハロゲンを示し、R1、R2、R3、Xはいずれ
の組合せの化合物であつても良い。3−クロロ−
4−ヒドロキシフエニル酢酸から4−ヒドロキシ
フエニル酢酸又はそのアルキルエステルを製造す
る場合が好適に実施される。上記の場合、3−ク
ロロ−4−ヒドロキシフエニル酢酸はグリオキシ
ル酸とO−クロロフエノールとからマンデル酸誘
導体を経て容易に調製が可能であり、本発明の方
法は従来法に比べて原料の価格面、及び目的物の
収率面で利点を有しており、その有用性は極めて
高い。
本発明においては一般式
Dehalogenation of halogen-substituted phenylacetic acids represented by the formula is completely unknown. In the present invention, phenylacetic acids useful as pharmaceutical intermediates can be easily obtained from such raw materials by dehalogenation, and the technology is novel and has extremely high industrial utility value. In the present invention, R 1 , R 2 and R 3 are each hydrogen,
Indicates a lower alkyl group such as a methyl group, ethyl group, propyl group, butyl group. Further, X represents a halogen such as chloro or bromine, and R 1 , R 2 , R 3 and X may be any combination of compounds. 3-chloro-
The production of 4-hydroxyphenylacetic acid or an alkyl ester thereof from 4-hydroxyphenylacetic acid is preferably carried out. In the above case, 3-chloro-4-hydroxyphenylacetic acid can be easily prepared from glyoxylic acid and O-chlorophenol via a mandelic acid derivative, and the method of the present invention has lower raw material costs than conventional methods. It has advantages in terms of surface area and yield of the target product, and its usefulness is extremely high. In the present invention, the general formula
【式】で示されるハロゲ
ン置換フエニル酢酸類を脱ハロゲン化するには接
触水素化分解法が有利に実施される。
本発明において上記接触水素化分解を行なうに
際しては系中に強酸を共存させることが必要であ
る。
従来の知見によればベンゼン核のハロゲンを接
触水素化分解により脱ハロゲンする場合には塩基
の存在が収率面で好ましいことが知られている
が、本発明において接触水素化分解を行うに当つ
てはかかる従来の知見とは全く逆に、強酸を系に
存在させることが不可欠の要件であり、むしろ塩
基の存在はフエニル酢酸類の収率を低下させる原
因となる。この点本発明のハロゲン置換フエニル
酢酸類の脱ハロゲンは従来の脱ハロゲン反応とそ
の機構を異にする特異な現象と考えられる。
更に、接触水素分解法を行なうに当つてはラネ
ーニツケル等のニツケル系触媒、パラジウム炭素
等のパラジウム系触媒、又は白金系触媒を用いる
ことが必要である。
本発明においては溶媒の選定も重要な要件であ
り、その種類によつて目的物の収率が大巾に変わ
る。好適な溶媒としては、水溶媒、メタノール、
エタノール等の低級アルコール溶媒、及びこれら
の混合溶媒があげられる。該溶媒には更に1%〜
等量程度の酢酸、酢酸エステル、あるいはエーテ
ル等相溶性のある溶媒を混合することも可能であ
る。特にアルコール溶媒に1%〜等量程度の水又
は酢酸を添加する場合、アルコール溶媒単独使用
に比べて反応速度が向上する効果が得られる。
反応は常圧又は加圧下で実施出来る。又、強酸
としては塩酸、硫酸、オルトリン酸、ポリリン
酸、過塩素酸、過臭素酸、臭化水素酸、等の無機
酸あるいはメタンスルホン酸、ベンゼンスルホン
酸、トルエンスルホン酸等の有機酸が例示され
る。かかる強酸の中でも硫酸が好適に使用され
る。強酸はハロゲン置換フエニル酢酸類1モルに
対し0.05〜0.50モルの範囲で使用される。反応温
度は室温〜100℃なかんずく50〜80℃が好適であ
り、反応時間は1〜10時間の範囲から選択するの
が好ましい。
かくして脱ハロゲンが終了した後は、常法に従
つて触媒成分を除去し、反応液より4−ヒドロキ
シフエニル酢酸類等の脱ハロゲン化物を溶媒抽出
する。抽出液から溶媒を除去すれば結晶状又はオ
イル状の目的物が得られる。ついで必要に応じて
精製処理を実施出来る。
本発明によれば例えば4−ヒドロキシフエニル
酢酸又はそのアルキルエステルが3−クロロ−4
−ヒドロキシフエニル酢酸に対して90%以上の収
率で得られ、その工業的な利用価値は極めて大で
あると言える。
次に実例を挙げて本発明の方法を更に詳しく説
明する。以下「%」となるのは特にことわりのな
い限り重量基準である。
実例 1
振とう式耐圧反応器中でメタノール10ml中に3
−クロロ−4−ヒドロキシフエニル酢酸2.5gを
溶解したのち、95%硫酸0.175mlを添加した。次
に5%パラジウム/炭素触媒を260mg添加し、反
応器を密閉し、窒素ガス置換後、62℃まで昇温す
る。次いで水素ガス置換し、水素圧を5Kg/cm2に
保ちながら65〜67℃の温度にて撹拌下に4.5時間
接触水素化分解を行つた。
反応終了後、室温まで冷却し、水素ガスをパー
ジし、触媒を別した。液を減圧下に濃縮して
メタノールを留去し、残渣に飽和食塩水10mlを加
えた後、酢酸エチル30mlで抽出を行つた。酢酸エ
チルを留去すると淡褐色のオイル状物が2.1g得
られた。
得られたオイル状物についてガスクロマトグラ
ム、赤外線吸収スペクトル、NMRスペクトルを
測定したところ標品の4−ヒドロキシフエニル酢
酸メチルのそれと一致した。4−ヒドロキシフエ
ニル酢酸の収率は3−クロロ−4−ヒドロキシフ
エニル酢酸に対して94.4%であつた。
実例 2
5%パラジウム/炭素の使用量を133mg、水素
圧を6Kg/cm2、反応温度を70〜77℃、反応時間を
5時間に変更した以外は実例1と同様の実験を行
つた。
4−ヒドロキシフエニル酢酸メチルが90%の収
率で得られた。
実例 3〜4
実例2においてメタノールを水に(実例3)、
及び水−酢酸(重量比1:1)に(実例4)変更
した以外は同例と同じ実験を行つた。
4−ヒドロキシフエニル酢酸が実例3では95
%、実例4では90%の収率が得られた。Catalytic hydrogenolysis is advantageously carried out to dehalogenate the halogen-substituted phenylacetic acids represented by the formula. When carrying out the catalytic hydrogenolysis in the present invention, it is necessary to coexist a strong acid in the system. According to conventional knowledge, it is known that the presence of a base is preferable in terms of yield when dehalogenating the halogen of the benzene nucleus by catalytic hydrogenolysis. Quite contrary to such conventional knowledge, the presence of a strong acid in the system is an essential requirement; rather, the presence of a base causes a decrease in the yield of phenylacetic acids. In this respect, the dehalogenation of the halogen-substituted phenylacetic acids of the present invention is considered to be a unique phenomenon that differs in its mechanism from conventional dehalogenation reactions. Furthermore, in carrying out the catalytic hydrogen cracking method, it is necessary to use a nickel-based catalyst such as Raney nickel, a palladium-based catalyst such as palladium on carbon, or a platinum-based catalyst. In the present invention, the selection of the solvent is also an important requirement, and the yield of the target product varies greatly depending on the type of solvent. Suitable solvents include water, methanol,
Examples include lower alcohol solvents such as ethanol, and mixed solvents thereof. The solvent also contains 1% to
It is also possible to mix approximately equal amounts of compatible solvents such as acetic acid, acetic ester, or ether. In particular, when water or acetic acid is added to the alcohol solvent in an amount of about 1% to the equivalent, the reaction rate is improved compared to when the alcohol solvent is used alone. The reaction can be carried out at normal pressure or under elevated pressure. Examples of strong acids include inorganic acids such as hydrochloric acid, sulfuric acid, orthophosphoric acid, polyphosphoric acid, perchloric acid, perbromic acid, and hydrobromic acid, and organic acids such as methanesulfonic acid, benzenesulfonic acid, and toluenesulfonic acid. be done. Among such strong acids, sulfuric acid is preferably used. The strong acid is used in an amount of 0.05 to 0.50 mol per mol of the halogen-substituted phenylacetic acid. The reaction temperature is preferably room temperature to 100°C, particularly 50 to 80°C, and the reaction time is preferably selected from the range of 1 to 10 hours. After the dehalogenation is thus completed, the catalyst component is removed according to a conventional method, and the dehalogenated products such as 4-hydroxyphenylacetic acids are extracted with a solvent from the reaction solution. By removing the solvent from the extract, the desired product in the form of crystals or oil can be obtained. Purification treatment can then be carried out if necessary. According to the present invention, for example, 4-hydroxyphenylacetic acid or its alkyl ester is
It can be obtained with a yield of 90% or more based on -hydroxyphenylacetic acid, and its industrial utility value can be said to be extremely large. Next, the method of the present invention will be explained in more detail by giving examples. In the following, "%" is based on weight unless otherwise specified. Example 1 3 in 10 ml of methanol in a shaking pressure reactor
After dissolving 2.5 g of -chloro-4-hydroxyphenylacetic acid, 0.175 ml of 95% sulfuric acid was added. Next, 260 mg of 5% palladium/carbon catalyst is added, the reactor is sealed, and after purging with nitrogen gas, the temperature is raised to 62°C. Next, hydrogen gas was replaced, and catalytic hydrogenolysis was carried out at a temperature of 65 to 67° C. for 4.5 hours with stirring while maintaining the hydrogen pressure at 5 kg/cm 2 . After the reaction was completed, it was cooled to room temperature, hydrogen gas was purged, and the catalyst was separated. The liquid was concentrated under reduced pressure to remove methanol, and 10 ml of saturated brine was added to the residue, followed by extraction with 30 ml of ethyl acetate. When ethyl acetate was distilled off, 2.1 g of a light brown oil was obtained. Gas chromatogram, infrared absorption spectrum, and NMR spectrum of the obtained oil were measured, and the results were consistent with those of standard 4-hydroxyphenylacetate methyl. The yield of 4-hydroxyphenylacetic acid was 94.4% based on 3-chloro-4-hydroxyphenylacetic acid. Example 2 An experiment similar to Example 1 was conducted except that the amount of 5% palladium/carbon used was 133 mg, the hydrogen pressure was 6 Kg/cm 2 , the reaction temperature was 70 to 77°C, and the reaction time was 5 hours. Methyl 4-hydroxyphenylacetate was obtained with a yield of 90%. Examples 3-4 In Example 2, methanol is added to water (Example 3),
and water-acetic acid (weight ratio 1:1) (Example 4) The same experiment as in the same example was conducted except that the mixture was changed to water-acetic acid (weight ratio 1:1). 4-Hydroxyphenylacetic acid is 95 in Example 3.
%, and in Example 4 a yield of 90% was obtained.
Claims (1)
ルキル基〕で表されるハロゲン置換フエニル酢酸
類を強酸の存在下に接触水素化分解を行つて脱ハ
ロゲンすることを特徴とする一般式
【式】〔ここでR1、R2、 R3は前記と同様〕で表されるフエニル酢酸類の
製造法。[Claims] 1. Halogen-substituted phenylacetic acids represented by the general formula [Formula] [where X: halogen, R 1 , R 2 , R 3 ; hydrogen or lower alkyl group] are brought into contact in the presence of a strong acid. A method for producing phenylacetic acids represented by the general formula [where R 1 , R 2 , and R 3 are the same as above], which comprises dehalogenating by hydrogenolysis.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP9525579A JPS5618936A (en) | 1979-07-25 | 1979-07-25 | Production of phenylacetic acid |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP9525579A JPS5618936A (en) | 1979-07-25 | 1979-07-25 | Production of phenylacetic acid |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS5618936A JPS5618936A (en) | 1981-02-23 |
JPS63421B2 true JPS63421B2 (en) | 1988-01-07 |
Family
ID=14132644
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP9525579A Granted JPS5618936A (en) | 1979-07-25 | 1979-07-25 | Production of phenylacetic acid |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS5618936A (en) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3151589A1 (en) * | 1981-12-28 | 1983-07-07 | Basf Ag, 6700 Ludwigshafen | DIETHER OF M- OR P-HYDROXYPHENOLS AND METHOD FOR PRODUCING THE DIETHER OR MONOETHER OF M- OR P-HYDROXYPHENOLS |
FR2686877B1 (en) * | 1992-01-31 | 1995-03-24 | Hoechst France | PROCESS FOR THE PREPARATION OF ORTHOHYDROXYPHENYLACETIC ACID. |
JP2813796B2 (en) * | 1995-11-10 | 1998-10-22 | 立体写真像株式会社 | Relief photo statue production method |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS54125635A (en) * | 1978-02-20 | 1979-09-29 | Diamalt Ag | Manufacture of 44hydroxyphenylacetic acid |
-
1979
- 1979-07-25 JP JP9525579A patent/JPS5618936A/en active Granted
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS54125635A (en) * | 1978-02-20 | 1979-09-29 | Diamalt Ag | Manufacture of 44hydroxyphenylacetic acid |
Also Published As
Publication number | Publication date |
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JPS5618936A (en) | 1981-02-23 |
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